Although knee osteoarthritis (OA) is a major cause of disability, few risk factors for its progression have been identified. Varus-valgus alignment is a key determinant of load distribution and a potent risk factor for knee OA progression. Full-limb x-ray, the gold standard test, has substantial drawbacks, which inhibit wide use in studies, screening programs, or in clinic patients. A physical exam approach provides a key opportunity to measure alignment without radiation exposure, cost, or equipment requirements. We have developed a novel physical exam approach to measure alignment. The current proposal capitalizes on the infrastructure of the Mechanical Factors in Arthritis of the Knee study of 300 persons with knee OA. We test three hypotheses: 1) Physical exam assessment of varus-valgus malalignment (PE-M) is sensitive and specific as a measure of full-limb x-ray malalignment (XR-M); 2) Increased varus PE-M and increased valgus PE-M are associated with greater knee OA disease severity in the medial and lateral compartment respectively; 3) Greater varus PE-M and greater valgus PE-M at baseline are associated with greater subsequent medial and lateral tibiofemoral cartilage volume loss respectively between baseline and 2 years later.